The overall goal of the Experimental Therapeutics (ET) Program is the development of novel mechanism-driven anticancer therapies through an improved understanding of molecular pathways in normal cells and cancer cells and insights into mechanisms involved in drug resistance. To achieve this goal, the Program is organized into three interacting (interactive) research themes that span the spectrum of basic, translational and clinical science: Angiogenesis and Metastasis, Cell Survival and Drug Resistance, and Gene expression and Molecular Targets, In addition to these themes, the ET program has two overarching missions. First, to be the conduit for bringing scientific findings from other CCSG programs into the clinic. As such, the Phase I and ET Drug Development expertise provides an Institute-wide resource for drug discovery methods, preclinical efficacy studies, IND-enabling toxicology, IND submission support, PK/PD modeling, and clinical trial conduct and management. Secondly, the ET Program is committed to training the next generation of clinician-scientists with expertise in all phases of drug development. The Program is co-led by Drs. Alex Adjei, and William Cance. Dr. Adjei is an internationally recognized clinician scientist with expertise in drug development, phase l/ll clinical trials of novel cancer agents and lung cancer. As the director of the Phase I unit, his leadership has been instrumental in building the drug development team. His research interests are in targeting cell survival pathways for cancer therapy in lung cancer. Dr. Cance is a highly regarded cancer surgeon and translational scientist with long-standing interests in angiogenesis and tumor metastasis. He has an ROl-funded program evaluating FAK inhibitors for cancer therapy. The complementary expertise of the leadership team facilitates the integration of basic, translational and clinical science by providing venues to promote discussion of research, formation of basic science-clinical partnerships, and providing guidance to membership for available research funding. The Program consists of 25 members from 7 departments. 541 publications are the product of ET members (2008-2013), with 23% of the publications as intra-programmatic and 22% inter-programmatic. 34 publications were in journals with Impact Factor >10. The ET Program has translated recent preclinical findings into 12 ongoing clinical trials. There were 326 patients enrolled to treatment trials in CY2012 compared with 453 patients in CY2008. Current annual total peer-reviewed Program funding is $10.3M, of which $9.3M is from NCI, and the total extramural research funding is $14.4M.